Top KOLs Discussing HORIZON-Breast06
HORIZON-Breast06: Trastuzumab rezetecan in metastatic HER2low breast cancer n=551 PFS chemo-naive: 16.6 vs 6.8 mo HR 0.25 PFS consistent in HR+ vs HR- (HR 0.34 and HR 0.24) OS immature ILD 2.5% @OncoAlert #ESMO2026 https://t.co/SwCRjdV8MO
— Sara Tolaney (@stolaney1) Oct 23, 2026
Source note: per the LBA13 abstract and presentation, PFS HR was 0.24 in HR-positive and 0.34 in HR-negative disease.
HORIZON-Breast06 Key Slides & Visuals
HORIZON-Breast06 Top Tweets
#ESMO26 | HORIZON-Breast06 HER2-low mBC after ≥1 prior line of chemo for metastatic disease, or in the first-line chemo setting after prior ET (if HR+). Trastuzumab rezetecan vs. physician’s choice of chemo PFS: 16.4 vs 6.8 mo (HR 0.27) ORR: 75.5% vs 41.2% Grade ≥3 TRAEs: 84.1% vs 67.9% ILD: 2.5%.
Source note: the LBA13 abstract enrolled patients with ≤1 (not ≥1) prior line of chemotherapy for metastatic disease. PFS 16.4 vs 6.8 months (HR 0.27) and ORR 75.5% vs 41.2% are overall-population figures.
🇨🇳HORIZON-Breast06: Trastuzumab rezatecan widely outperformed chemo in endocrine-refractory HR+ MBC (PFS 16.6 vs 6.8 months, HR 0.25, p=0<0.01). Definitely passes the truck test. No significant OS, likely due to crossover of some patients to TOPO1 ADCs. #ESMO26 #ESMOAmbassadors https://t.co/u7TsssjoiN
Source note: HORIZON-Breast06 enrolled HER2-low disease regardless of HR status (73.0% HR-positive, 27.0% HR-negative); 16.6 vs 6.8 months (HR 0.25) is the chemo-naive co-primary population (LBA13).
#ESMO26 | HORIZON-Breast06 Impressive PFS benefit✨️ In HER2-low mBC, trastuzumab rezetecan significantly improved PFS vs chemo: 16.4 vs 6.8 mo Benefit was consistent in HR+ (HR 0.24) and HR− (0.34) pts OS remains immature, but an encouraging trend is emerging (HR 0.67). https://t.co/HvdSAeLquN https://t.co/uARxyCOkHl
Source note: 16.4 vs 6.8 months is the overall-population co-primary (HR 0.27); the chemo-naive co-primary was 16.6 vs 6.8 months (HR 0.25). OS HR 0.67 (95% CI 0.48-0.94) is the immature overall-population OS shown on the LBA13 presentation slide.
中国からのHER2-ADC trastuzumab-rezetecanのHER2-lowへの1st line/2nd lineでのPhase3 HORIZON-Breast06試験。 有意にPFSを延長。OSも延長傾向。すごいな... #ESMO26 https://t.co/eN7GdcPlFi
HORIZON-Breast06: Trastuzumab Rezetecan in HER2-Low Metastatic #BreastCancer — A Major PFS Benefit, With OS and Long-Term Safety Requiring Further Follow-Up @OncoAlert #ESMO26 @myESMO #Bcsm https://t.co/X8ZCODantr
HORIZON-Breast06: Trastuzumab rezetecan in metastatic HER2low breast cancer n=551 PFS chemo-naive: 16.6 vs 6.8 mo HR 0.25 PFS consistent in HR+ vs HR- (HR 0.34 and HR 0.24) OS immature ILD 2.5% @OncoAlert #ESMO2026 https://t.co/SwCRjdV8MO
Source note: per the LBA13 abstract and presentation, PFS HR was 0.24 in HR-positive and 0.34 in HR-negative disease.
HORIZON-Breast06 confirms benefit of trastuzumab *rezetecan* in a DB06-like patient population—HER2low, chemo-naive #ESMO26 @OncoAlert https://t.co/oQ56NjDGq4
Trastuzumab rezetecan improves PFS in chemo-naive and chemo pretreated HER2 low MBC - low incidence of ILD #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO @JAMA_current https://t.co/c6WGevRG07
Oral abstract #BreastCancer session at #ESMO26: simultaneously published @JAMA_current results from #HORIZONbreast06 trial showing impressive activity of #TrastuzumabRezetecan in patients with HER2-low advanced disease @OncoAlert @myESMO https://t.co/S3SPEIW9ih
At #ESMO26 proffered paper session 1️⃣ on #breastcancer Trastuzumab rezetecan in HER2-low aBC vs CT of physician’s choice ⬆️ PFS in chemo-naive and overall patients Consistent benefit according to HR status Simultaneous publication on @JAMA_current @OncoAlert https://t.co/g77mCc7dEx
Trastuzumab rezetecan in #HER2 low #bcsm (HORIZON-Br06) vs. TPC chemo 📍HER-2 low (TNBC or HR+) w/ up to 1 prior chemo 👏 PFS improved 6.8 to 16.6 mo (HR 0.25) in chemo naive 🟰 PFS ⬆️ in HR+ & HR- & across subgroups Neutropenia most common AE #ESMO26 #ESMOAmbassadors https://t.co/SXmCMvmDPy
Impressive results with trastuzumab rezetecan in the first-line treatment of HR+ MBC! Differences vs T-DXd: 🎯Lower DAR (5.7 vs 8) 🎯Less ILD, but greater myelosuppression Similarity to T-DXd: 🎯Both are HER2-targeted ADCs with a TOP1 inhibitor payload #ESMO26 https://t.co/dl6O4mEisW
🔥 New ADCs in breast cancer, or just more “me-too” ADCs? Trastuzumab rezetecan and rolditamig deuderuxtecan in HER2low mBC: impressive efficacy and good tolerability (Chinese populations only) Are they better than T-DXd? We don’t know HEAD-TO-HEAD trials are needed! #ESMO26 https://t.co/ib2mTJcolk
Trastuzumab rezetecan shows a PFS benefit in HER2-low metastatic breast cancer, both before and after chemotherapy, with a low reported incidence of ILD. #ESMO26 #ESMOAmbassadors #ESMOcommunity @myESMO @Larvol @OncoAlert https://t.co/H3KMB59u2w
Three HER2 ADCs now in HER2-low MBC. At #ESMO26, HORIZON-Breast06 & APEX-Breast01 both beat chemo on PFS (HR ~0.25–0.29). But as @BarbaraPistill2 noted: same payload class as Tdxd, tested vs chemo not the standard. Head-to-head ADC trials needed. #ESMOAmbassadors @myESMO https://t.co/Yntya2iiR3
Cowabunga! 🌊 Riding the Metastatic Breast Cancer Wave 🏄🏻♂️🤙🏻 from #ESMO26 HORIZON-Breast06: trastuzumab rezetecan vs chemo in HER2-low disease. Progression-free survival 16.4 vs 6.8 mo, hazard ratio 0.27. HER2-low is ADC territory now. Which antibody-drug conjugate, and when? @OncoAlert @Larvol
確かに、中国からのAPEX breast01も、HORIZON breast06も、PFSのHRや、試験治療群のPFS中央値はとても新規ADCで良好に見えて、T-DXdより良いのかもと期待はしてしまうけれど、あくまでhead to headの結果がないと、エンハーツを超えた治療という冠は与えられないね。 #ESMO26 https://t.co/3UBkeLtUtT
🚨 ESMO 2026 | HORIZON-Breast06 (Phase III) Impressive results with trastuzumab rezetecan (HER2 ADC) vs physician’s choice chemo in HER2-low mBC. 🔹 mPFS: 16.6 vs 6.8 mo (HR 0.25; P<0.001) in chemo-naïve pts 🔹 ORR: 76% vs 43.3% 🔹 HR+: mPFS 16.4 vs 6.7 mo (HR 0.24) 🔹 HR−: mPFS 16.5 vs 6.8 mo (HR 0.34) 🔹 mDoR: 15.3 vs 6.9 mo ⚠️ Toxicity: Significant G≥3 myelosuppression (anemia 42.8%, neutropenia 65.2%, thrombocytopenia 35.9%). ILD reported in 2.5% (any grade). #ESMO26 #BreastCancer #HER2Low #ADC @OncoAlert #bcsm
First breast session at #ESMO26 highlights how China is developing novel drugs at rapid speed. Positive PFS results with HER2-directed ADCs (HORIZON-Breast06 + APEX-Breast01), but neither compare to current SoC of T-DXd. Fights for market share, but does it push the needle?
About the HORIZON-Breast06 Trial
HORIZON-Breast06 asked whether a HER2-directed antibody-drug conjugate could replace single-agent chemotherapy in HER2-low advanced breast cancer, including in patients who had not yet received chemotherapy for metastatic disease. Trastuzumab rezetecan (SHR-A1811) is developed by Jiangsu HengRui Medicine. The trial enrolled 551 patients in China with HER2-low disease, hormone receptor-positive or -negative, after endocrine therapy for HR-positive disease and with no more than one prior chemotherapy line in the metastatic setting. Randomization was stratified by prior chemotherapy lines, HER2 IHC score and HR status/prior CDK4/6 inhibitor. The results were presented by Ying Fan, MD, in the ESMO 2026 Proffered Paper session (LBA13) and published simultaneously in JAMA.
HORIZON-Breast06 confirms benefit of trastuzumab *rezetecan* in a DB06-like patient population—HER2low, chemo-naive #ESMO26 @OncoAlert https://t.co/oQ56NjDGq4
— Stephanie Graff, MD, FACP, FASCO (@DrSGraff) Oct 23, 2026
Trial Methodology & Results
Study Design
Randomized 1:1, open-label, multicenter phase 3 (NCT05814354; SHR-A1811-III-306). 551 patients randomized (277 vs 274).
Population
Centrally confirmed HER2-low (IHC 1+ or IHC 2+/ISH-) advanced breast cancer; ≤1 prior chemotherapy line for metastatic disease; prior endocrine therapy required if HR-positive. 81.5% chemo-naive, 73.0% HR-positive, 64.8% prior CDK4/6 inhibitor.
Interventions
Trastuzumab rezetecan 6.4 mg/kg IV every 3 weeks vs physician’s choice of chemotherapy: taxanes, eribulin, capecitabine or gemcitabine.
Endpoints
Co-primary: PFS by BICR in chemo-naive patients and in all patients. Key secondary: OS (overall, chemo-naive); PFS in chemo-treated patients.
Lead Author / Presenter
Ying Fan, MD (Beijing, China); senior author Binghe Xu, MD, PhD (JAMA).
Data Cut
March 20, 2026. Median follow-up 18.0 months (95% CI 16.8–19.3).
Co-primary endpoint: progression-free survival (BICR)
Trastuzumab rezetecan prolonged PFS in both co-primary populations (LBA13 abstract, data cutoff Mar 20, 2026). The presentation and JAMA report the same medians and HRs with P<.001.
| PFS by BICR | Chemo-naive: T-Rez (N=225) | Chemo-naive: chemo (N=224) | Overall: T-Rez (N=277) | Overall: chemo (N=274) |
|---|---|---|---|---|
| Events, n (%) | 91 (40.4) | 146 (65.2) | 130 (46.9) | 185 (67.5) |
| Median (95% CI), months | 16.6 (14.0–19.4) | 6.8 (5.7–7.0) | 16.4 (14.0–16.8) | 6.8 (5.7–6.9) |
| 12-month PFS rate, % (95% CI) | 65.2 (57.6–71.8) | 18.9 (12.8–25.8) | 63.1 (56.4–69.1) | 18.0 (12.7–24.1) |
| HR (95% CI); one-sided P | 0.25 (0.19–0.33); P<0.0001 | 0.27 (0.21–0.34); P<0.0001 | ||
By HR status: HR-positive 16.4 vs 6.7 months (HR 0.24; 95% CI 0.18–0.33); HR-negative 16.5 vs 6.8 months (HR 0.34; 95% CI 0.22–0.54) (LBA13 presentation, data cutoff Mar 20, 2026).
PFS HR 0.25 chemo-naive · 0.27 overallJAMA, doi:10.1001/jama.2026.21372 · LBA13 abstract (as posted)
Trastuzumab rezetecan in #HER2 low #bcsm (HORIZON-Br06) vs. TPC chemo 📍HER-2 low (TNBC or HR+) w/ up to 1 prior chemo 👏 PFS improved 6.8 to 16.6 mo (HR 0.25) in chemo naive 🟰 PFS ⬆️ in HR+ & HR- & across subgroups Neutropenia most common AE #ESMO26 #ESMOAmbassadors https://t.co/SXmCMvmDPy
— Erika Hamilton, MD, FASCO (@ErikaHamilton9) Oct 23, 2026
Overall survival (immature)
All patients: 66 (23.8%) vs 77 (28.1%) deaths; 12-month OS 90.6% vs 81.4%; HR 0.67 (95% CI 0.48–0.94). Chemo-naive: 43 (19.1%) vs 55 (24.6%) deaths; 12-month OS 92.0% vs 83.0%; HR 0.62 (95% CI 0.41–0.93) (LBA13 presentation, data cutoff Mar 20, 2026). The abstract reports OS as immature with a trend favoring trastuzumab rezetecan. An interim OS analysis is planned at 274 events (~52% maturity) and the final analysis at 392 events (~74%).
ClinicalTrials.gov NCT05814354#ESMO26 | HORIZON-Breast06 Impressive PFS benefit✨️ In HER2-low mBC, trastuzumab rezetecan significantly improved PFS vs chemo: 16.4 vs 6.8 mo Benefit was consistent in HR+ (HR 0.24) and HR− (0.34) pts OS remains immature, but an encouraging trend is emerging (HR 0.67). https://t.co/HvdSAeLquN https://t.co/uARxyCOkHl
— Yakup Ergün (@dr_yakupergun) Oct 23, 2026
Source note: 16.4 vs 6.8 months is the overall-population co-primary (HR 0.27); the chemo-naive co-primary was 16.6 vs 6.8 months (HR 0.25). OS HR 0.67 (95% CI 0.48-0.94) is the immature overall-population OS shown on the LBA13 presentation slide.
Response
ORR 76.0% vs 43.3% in chemo-naive patients and 75.5% vs 41.2% overall (LBA13 abstract, data cutoff Mar 20, 2026); 73.1% vs 32.0% in chemo-treated patients. Median duration of response 15.3 vs 6.9 months chemo-naive, 10.4 vs 6.1 months chemo-treated and 15.0 vs 6.8 months overall (LBA13 presentation, data cutoff Mar 20, 2026).
ORR 75.5% vs 41.2% overallJAMA, doi:10.1001/jama.2026.21372
Safety
Grade ≥3 treatment-related adverse events occurred in 84.1% (232/276) with trastuzumab rezetecan and 67.9% (184/271) with chemotherapy. Interstitial lung disease was reported in 7 patients (2.5%) with trastuzumab rezetecan (LBA13 abstract, data cutoff Mar 20, 2026; JAMA); per JAMA, 3 (1.1%) were grade ≥3, none grade 5, and no ILD occurred with chemotherapy. The most common grade ≥3 events were hematologic: neutrophil count decreased 65.2% vs 54.2%, white blood cell count decreased 56.5% vs 35.4%, anemia 42.8% vs 4.8% and platelet count decreased 35.9% vs 1.8% (LBA13 presentation, data cutoff Mar 20, 2026).
ILD 2.5%; grade ≥3 TRAEs 84.1% vs 67.9%JAMA, doi:10.1001/jama.2026.21372
🚨 ESMO 2026 | HORIZON-Breast06 (Phase III) Impressive results with trastuzumab rezetecan (HER2 ADC) vs physician’s choice chemo in HER2-low mBC. 🔹 mPFS: 16.6 vs 6.8 mo (HR 0.25; P<0.001) in chemo-naïve pts 🔹 ORR: 76% vs 43.3% 🔹 HR+: mPFS 16.4 vs 6.7 mo (HR 0.24) 🔹 HR−: mPFS 16.5 vs 6.8 mo (HR 0.34) 🔹 mDoR: 15.3 vs 6.9 mo ⚠️ Toxicity: Significant G≥3 myelosuppression (anemia 42.8%, neutropenia 65.2%, thrombocytopenia 35.9%). ILD reported in 2.5% (any grade). #ESMO26 #BreastCancer #HER2Low #ADC @OncoAlert #bcsm
— Aydah AlAwadhi, MD 🇦🇪 (@Aydah_AlAwadhi) Oct 23, 2026
HORIZON-Breast06 in the News
HORIZON-Breast06 Questions
What is the HORIZON-Breast06 trial?
HORIZON-Breast06 (NCT05814354, study code SHR-A1811-III-306) is a randomized, open-label, multicenter phase 3 trial in China comparing trastuzumab rezetecan (SHR-A1811, 6.4 mg/kg IV every 3 weeks) with physician's choice of chemotherapy (taxanes, eribulin, capecitabine or gemcitabine) in 551 patients with HER2-low (IHC 1+ or IHC 2+/ISH-) advanced breast cancer who had received no more than one prior line of chemotherapy for metastatic disease. The co-primary endpoints were PFS by blinded independent central review in chemo-naive patients and in all patients.
What did HORIZON-Breast06 show?
Per the ESMO 2026 LBA13 abstract (data cutoff March 20, 2026), median PFS by BICR was 16.6 vs 6.8 months in chemo-naive patients (HR 0.25, 95% CI 0.19-0.33; one-sided P<0.0001) and 16.4 vs 6.8 months in all patients (HR 0.27, 95% CI 0.21-0.34; P<0.0001). ORR was 75.5% vs 41.2% overall. OS was immature (overall-population HR 0.67, 95% CI 0.48-0.94, on the presentation slide). Grade 3 or higher treatment-related adverse events occurred in 84.1% vs 67.9%, and interstitial lung disease in 7 patients (2.5%) on trastuzumab rezetecan.
Is trastuzumab rezetecan FDA approved?
No. Trastuzumab rezetecan is not FDA or EMA approved, and its use in HER2-low breast cancer is investigational. Its only approval found is in China: in May 2025 the NMPA approved it (Avida) for adults with previously treated, unresectable locally advanced or metastatic HER2 (ERBB2)-mutant non-small cell lung cancer (Hoy, Drugs 2026; PMID 41138046).
How is HORIZON-Breast06 different from HORIZON-Breast01?
Both test trastuzumab rezetecan, in different populations. HORIZON-Breast06 enrolled HER2-low advanced breast cancer and compared it with chemotherapy. HORIZON-Breast01 (NCT05424835) enrolled HER2-positive metastatic breast cancer and compared it with pyrotinib plus capecitabine.
How does trastuzumab rezetecan compare with trastuzumab deruxtecan in HER2-low disease?
There is no head-to-head trial. HORIZON-Breast06 compared trastuzumab rezetecan with chemotherapy. The accompanying JAMA editorial (Mosele and Andre) states that its place in care remains uncertain because trastuzumab deruxtecan is already approved in a similar setting and no head-to-head comparison is available.